X-linked recessive mental retardation has been estimated to cause 5-36% of all mental retardation. Among both institutionalized and non-institutionalized retarded children there is an excess of approximately 50% males. Although originally thought to be rare several hundered families are now known. In 1969, the present investigator reported a family with X-linked mental retardation in which all retarded males had an unusual X chromosome characterized by a secondary constriction or satellite-like appearance at the end of the long arm of the X. It is similar to regions called fragile sites in other chromosomes. With one exception all obligate carrier females in the family had the same X chromosome. In both males and females the marker X was demonstrated in only a minority of cells. Since that time some progress has been made in establishing optimal conditions for recognition of this marker X chromosome but in most laboratories the culture conditions currently used do not permit its detection or at best only variable detection in a small proportion of cells. In spite of this, however, 20 families are now known with the same marker chromosome and mental retardation in the males having the chromosome. The present project is designed to first optimize the conditions for detection of the marker X by a variety of alterations in the culture conditions, to further study the nature of the lesion by the use of a number of new cytogenetic techniques and finally to estimate the frequency of the marker X chromosome. The significance of this work lies in improved detection of a preventable form of mental retardation and in improved understanding of what is probably a new type of chrom somal abnormality. Finally, it is likely at least as frequent as XYY or XXY and in contrast to these abnormalities appears to be associated with mental retardation in all cases. Thus, it may be comparable to or even more frequent than Down syndrome as a cause of mental retardation.